dbSNP rs9408926: CNTRL:p.Leu1359Leu (chr9-121152596-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_007018.6(CNTRL):c.4075C>T(p.Leu1359Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 1,613,616 control chromosomes in the GnomAD database, including 2,267 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.039 ( 130 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2137 hom. )

Consequence

CNTRL
NM_007018.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.810

Publications

17 publications found

Variant links:

Genes affected

CNTRL (HGNC:1858): (centriolin) This gene encodes a centrosomal protein required for the centrosome to function as a microtubule organizing center. The gene product is also associated with centrosome maturation. One version of stem cell myeloproliferative disorder is the result of a reciprocal translocation between chromosomes 8 and 9, with the breakpoint associated with fibroblast growth factor receptor 1 and centrosomal protein 1. [provided by RefSeq, Jul 2008]

CNTRL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP7

Synonymous conserved (PhyloP=-0.81 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTRL	NM_007018.6 link	c.4075C>T	p.Leu1359Leu	synonymous_variant	Exon 26 of 44	ENST00000373855.7	NP_008949.4	Q7Z7A1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTRL	ENST00000373855.7 link	c.4075C>T	p.Leu1359Leu	synonymous_variant	Exon 26 of 44	5	NM_007018.6	ENSP00000362962.1		Q7Z7A1-1

Frequencies

GnomAD3 genomes

AF:

0.0387

AC:

5885

AN:

152124

Hom.:

130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0251

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.0158

Gnomad FIN

AF:

0.0501

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0549

Gnomad OTH

AF:

0.0364

GnomAD2 exomes

AF:

0.0378

AC:

9492

AN:

251192

AF XY:

0.0378

show subpopulations

Gnomad AFR exome

AF:

0.0240

Gnomad AMR exome

AF:

0.0189

Gnomad ASJ exome

AF:

0.0226

Gnomad EAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.0550

Gnomad NFE exome

AF:

0.0546

Gnomad OTH exome

AF:

0.0421

GnomAD4 exome

AF:

0.0506

AC:

73939

AN:

1461374

Hom.:

2137

Cov.:

AF XY:

0.0495

AC XY:

36014

AN XY:

727022

show subpopulations

African (AFR)

AF:

0.0219

AC:

734

AN:

33472

American (AMR)

AF:

0.0202

AC:

903

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0246

AC:

642

AN:

26130

East Asian (EAS)

AF:

0.00504

AC:

200

AN:

39684

South Asian (SAS)

AF:

0.0173

AC:

1492

AN:

86250

European-Finnish (FIN)

AF:

0.0557

AC:

2975

AN:

53416

Middle Eastern (MID)

AF:

0.0309

AC:

178

AN:

5768

European-Non Finnish (NFE)

AF:

0.0576

AC:

64013

AN:

1111558

Other (OTH)

AF:

0.0464

AC:

2802

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

3397

6794

10192

13589

16986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2382

4764

7146

9528

11910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0387

AC:

5887

AN:

152242

Hom.:

130

Cov.:

AF XY:

0.0365

AC XY:

2718

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0230

AC:

955

AN:

41546

American (AMR)

AF:

0.0250

AC:

383

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

AN:

3470

East Asian (EAS)

AF:

0.00367

AC:

AN:

5184

South Asian (SAS)

AF:

0.0156

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0501

AC:

531

AN:

10592

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0549

AC:

3734

AN:

68018

Other (OTH)

AF:

0.0374

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

282

564

846

1128

1410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0485

Hom.:

966

Bravo

AF:

0.0374

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0531

EpiControl

AF:

0.0507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.6

(source)

DANN

Benign

0.69

PhyloP100

-0.81

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over